Methods were developed for the determination of cAMP, cGMP, gamma-aminobutyric acid (GABA), substance P, endogenous opiate ligands, MHPG, dopamine-beta-hydroxylase and cortisol. Using these methods, it is possible to measure these compounds in a variety of tissues and under many physiological conditions. In particular, all of the above compounds may be measured in cerebrospinal fluid and plasma from human subjects. With the available cerebrospinal fluid from patients under study in the Sections of Psychobiology and Neuropsychopharmacology, no differences between patients with schizophrenia and affective disorders have yet been demonstrated for cAMP, cGMP and GABA. Extensive investigation of endogenous opiates and related peptides is underway using both a radioimmunoassay for beta-endorphin and opiate receptor assay for other endogenous opiates.